Abstract：Alzheimer′s disease (AD) is one of the most common diseases in the elderly, which can only be delayed by long-term medication. Oral administration and intravenous administration are the most common anti-AD treatments, there are obvious adverse reactions, frequent administration and other shortcomings, which can be solved by new preparation technology. Transdermal delivery and intranasal delivery can avoid the first passeffect of liver, improve bioavailability and effectively improve the fluctuation of blood concentration caused by sudden drug release.More convenient and efficient anti-AD preparations can be prepared by these two ways. In this paper, the research of preparations under different administration routes were reviewed in order to provide new ideas and references for the research and development of anti-AD drugs.
李杰雨, 姜海梅, 杨山景, 隋芳茜, 杨诗宇, 李凌军. 抗阿尔茨海默病药物不同给药途径下的制剂研究进展[J]. 中国药学杂志, 2022, 57(8): 589-594.
LI Jie-yu, JIANG Hai-mei, YANG Shan-jing, SUI Fang-qian, YANG Shi-yu, LI Ling-jun. Research Progress on Preparations of Anti-AD Drugs under Different Administration Routes. Chinese Pharmaceutical Journal, 2022, 57(8): 589-594.
ZHANG M X. The studies on the anti-Alzheimer′s disease fraction of acorus tatarinowii and its preliminary material basis [D]. Shanghai: China State Institute of Pharmaceutical Industry, 2016.
[2]
LU Y N. The main data of the Seventh National population Census announced that the total population maintained steady growth [N]. People′s Daily, 2021-05-12(1).
[3]
JIA L, DU Y, CHU L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study[J]. Lancet Public Health, 2020, 5(12):e661-e671.
[4]
KWON Y. Luteolin as a potential preventive and therapeutic candidate for Alzheimer′s disease [J]. Exp Gerontol, 2017, 95:39-43.
[5]
MARTIN R R,DE M L,AMBROSONE A, et al. Targeted nanoparticles for the treatment of Alzheimer′s disease [J]. Curr Pharm Des, 2017, 23(13):1927-1952.
[6]
LV Y M. Study of donepezil hydrochloride dispersible tablets [D]. Tianjin: Tianjin Medical University, 2017.
[7]
WANG Q Q, LV J L, HU Y C, et al. Pathogenesis and new therapeutic drugs of Alzheimer disease [J]. Chin Pharm J(中国药学杂志), 2020, 55(23):1939-1947.
[8]
ZHANG X L, ZENG J W, CHEN X, et al. Comparison and interpretation of Chinese and British guidelines about therapeutic drugs for Alzheimer′s disease [J]. Chin Gen Pract(中国全科医学), 2021, 24(12): 1454-1458.
[9]
GUO Y B, SHI J M, LIU H, et al. Research progress of amyloid β peptide as a drug target for Alzheimer′s disease [J]. Chin J Anat(解剖学杂志), 2021, 44(3): 242-246.
[10]
TOLAR M, ABUSHAKRA S, HEY J A, et al. Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer′s disease with potential for near term approval [J]. Alzheimers Res Ther, 2020, 12(1):95.
[11]
GUO Q Q, CHU E G, ZHONG Z G. Mechanism of traditional Chinese and western medicine research and treatment of senile dementia [J]. Asia-Pac Trad Med(亚太传统医药), 2015, 11(13): 41-44.
[12]
LI Y X.Bioavailability of single oral dose of galanthamine hydrobromide extended-release pellet capsule in dogs [J].J China Pharm(中国药房), 2009, 20(4): 261-262.
[13]
SANCHEZ L E, ETTCHETO M, EGEA M A, et al. New potential strategies for Alzheimer′s disease prevention: pegylated biodegradable dexibuprofen nanospheres administration to APPswe/PS1dE9 [J]. Nanomedicine, 2017, 13(3): 1171-1182.
[14]
CHEN Z M, LONG X Y. Research progress of different drug delivery routes in microparticle drug delivery system [J]. J Guangdong Pharm Univ(广东药学院学报), 2007,(6): 686-690.
[15]
QU Y D. Studies on the palliative effect of deproteinized calf blood extractives iniection on Alzheimer′s disease [D]. Changchun: Jilin University, 2019.
[16]
MA Y,XU R N. Study on the preparation technology of nimodipine freeze-dried powder injection [J]. Sci Technol Inf(科技信息),2007(26): 70-72.
[17]
LIU S K. Study on galanthamine long-acting sustained-release microsphere injection: China, 2009102302927[P]. 20131001.
[18]
CAI X Q. Studies on polymer thermogel of huperzine A [D]. Jinan: Shandong University, 2012.
[19]
XIANG N X, ZHANG Y, HE X Y, et al. Preparation and pharmacokinetic study of huperzine A phospholipid in situ-gel [J]. West China J Pharm Sci(华西药学杂志), 2017, 32(2): 143-146.
[20]
DONG H Y, ZHANG H, SHUAI Z F, et al. Effects of β-asarone and tenuigenin on activities of SOD, GSH, CAT, MDA and HO-1 in APP/PS1 double transgenic mice [J]. Nat Prod Res Dev(天然产物研究与开发), 2017, 29(9): 1551-1557.
[21]
SIAFAKA P I, BULBUL E O, MUTLU G, et al. Transdermal drug delivery systems and their potential in Alzheimer′s disease management [J]. CNS Neurol Disord Drug Targets. 2020, 19(5): 360-373.
[22]
ZHANG Z X, HONG Z, WANG Y P, et al. Rivastigmine patch in Chinese patients with probable Alzheimer′s disease: A 24-week, randomized, double-blind parallel-group study comparing rivastigmine patch (9.5 mg/24 h) with capsule (6 mg twice daily) [J]. CNS Neurosci Ther, 2016, 22(6): 488-496.
[23]
SALUJA S, KASHA PC, PATURI J, et al. A novel electronic skin patch for delivery and pharmacokinetic evaluation of donepezil following transdermal iontophoresis [J]. Int J Pharm, 2013, 453(2): 395-399.
[24]
WANG J S, WANG W Q, WANG C G, et al. Advances in studies on transdermal patch of Chinese materia medica [J]. Chin Tradit Herb Drugs(中草药), 2012, 43(5): 1028-1031.
[25]
CUI Y, GUO J, ZHANG L.Microemulsion and its application in different ways of drug administration [J]. J China Pharm(中国药房), 2010, 21(25): 2390-2393.
[26]
SHI J, CONG W, WANG Y, et al. Microemulsion-based patch for transdermal delivery of huperzine A and ligustrazine phosphate in treatment of Alzheimer′s disease [J]. Drug Dev Ind Pharm, 2012, 38(6): 752-761.
[27]
ZHU H M, LIU T, HE Q R, et al. Research progress of transdermal gel of traditional Chinese medicine [J]. Chin Tradit Pat Med(中成药), 2018, 40(8): 1811-1814.
[28]
WOO F Y, BASRI M, MASOUMI H R, et al. Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer′s disease [J]. Int J Nanomed, 2015, 10: 3879-3886.
[29]
MENDES I T, RUELA A L M, CARVALHO F C, et al. Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil [J]. Colloids Surf B Biointerfaces, 2019, 177: 274-281.
[30]
SETYA S, MADAAN T, RAZDAN BK, et al. Design and development of novel transdermal nanoemulgel for Alzheimer′s disease: pharmacokinetic, pharmacodynamic and biochemical investigations [J]. Curr Drug Deliv, 2019, 16(10): 902-912.
[31]
NGUYEN T T, PARK J H. Human studies with microneedles for evaluation of their efficacy and safety [J]. Expert Opin Drug Deliv, 2018, 15(3): 235-245.
[32]
WEI W, ZHAO F, MA Y L, et al. Research progress of nanodrug delivery system based on microneedles [J]. Chin Pharm J(中国药学杂志), 2021, 56(10): 785-789.
[33]
YAN Q, WANG W, WENG J, et al. Dissolving microneedles for transdermal delivery of Huperzine A for the treatment of Alzheimer′s disease [J]. Drug Deliv, 2020, 27(1): 1147-1155.
[34]
SONG L L. Study on the preparation technology and quality of donepezil hydrochloride tablets [D]. Jinan: Shandong University, 2016.
[35]
KIM J Y, HAN M R, KIM Y H, et al. Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer′s disease [J]. Eur J Pharm Biopharm, 2016, 105: 148-155.
[36]
KEARNEY M C, CAFFAREL S E, FALLOWS S J, et al. Microneedle-mediated delivery of donepezil: Potential for improved treatment options inAlzheimer′s disease [J]. Eur J Pharm Biopharm, 2016, 103: 43-50.
[37]
BAHADUR S, SACHAN N, HARWANSH R K, et al. Nanoparticlized system: promising approach for the management of Alzheimer′s disease through intranasal delivery [J]. Curr Pharm Des, 2020, 26(12): 1331-1344.
[38]
SUN Y, LI L, XIE H, et al. Primary studies on construction and evaluation of ion-sensitive in situ gel loaded with paeonol-solid lipid nanoparticles for intranasal drug delivery [J]. Int J Nanomed, 2020, 15: 3137-3160.
[39]
XIANG Y, LONGY, TAN Y J, et al. Application of new dosage forms and new techniques in nasal and cerebral targeted drug delivery system of effective components of traditional Chinese medicine [J]. Chin Tradit Pat Med(中成药), 2020, 42(4): 991-995.
[40]
CHEN X M.Experimental study on pharmacodynamics of Ginsenoside Rg1 nasal spray [J]. Chin J Exp Tradit Med Form(中国实验方剂学杂志), 2011, 17(10): 219-222.
[41]
CHEN X M.Effect of dosage form and administration route to distribution of Ginsenoside Rg1 in serum and brain of rats [J]. Chin J Exp Tradit Med Form(中国实验方剂学杂志), 2011, 17(14): 43-46.
[42]
XU X P, PAI Y F, HUANG Z J, et al. Preparation of nimodipine nanoemulsion for intranasal delivery and preliminary studies on its brain tissue targeting [J]. Chin Pharm J(中国药学杂志), 2012, 47(8): 594-598.
[43]
CHEN G. Studies on huperzine a microemulsion temperature/pH-sensitive in situ gel for nasal delievery [D]. Hefei: Anhui University of Chinese Medicine, 2016.
[44]
XU R X. Process, quality evaluation and rat brain targeting study of Shenqing nasal microemulsion [D]. Guangzhou: Guangzhou University of Chinese Medicine, 2013.
[45]
ESPINOZA LC, VACACELA M, CLARES B, et al. Development of a nasal donepezil-loaded microemulsion for the treatment of Alzheimer′s disease: in vitro and ex vivo characterization [J]. CNS Neurol Disord Drug Targets, 2018, 17(1): 43-53.
[46]
VIEIRA D B, GAMARRA L F. Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier [J]. Int J Nanomed, 2016, 11: 5381-5414.
[47]
ROSS C, TAYLOR M, FULLWOOD N, et al. Liposome delivery systems for the treatment of Alzheimer′s disease [J]. Int J Nanomed, 2018, 13: 8507-8522.
[48]
AL ASMARI A K, ULLAH Z, TARIQ M, et al. Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil [J]. Drug Des Devel Ther, 2016, 10: 205-215.
[49]
TAN Y Z. Study on drug delivery system of H102 peptide loaded PEG-PLGA nanoparticles [D].Tianjin: Tianjin Medical University, 2013.
[50]
ZHENG X, SHAO X, ZHANG C, et al. Intranasal H102 peptide-loaded liposomes for brain delivery to treat Alzheimer′s disease [J]. Pharm Res, 2015, 32(12): 3837-3849.
[51]
SHAO Y X.Development of nasal spray of H102 peptide to treat Alzheimer′s disease [D]. Shanghai: Fudan University, 2013.
[52]
TAN Y Z, SHAO Y X, CHEN J, et al. Preparation, characteristic and in vivo study of H102 loaded PEG-PLGA nanoparticles [J]. Chin Pharm J(中国药学杂志), 2014, 49(3): 216-220.
[53]
JIANG Y Y. The design of lactoferrin loaded HupAnanoemulsion and research of brain targeting mechanism via intranasal route [D]. Changchun: Jilin University, 2020.
[54]
MUNTIMADUGU E, DHOMMATI R, JAIN A, et al. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer′s disease [J]. Eur J Pharm Sci, 2016, 92: 224-234.
[55]
ELNAGGAR Y S R, ETMAN S M, ABDELMONSIF D A, et al. Intranasal Piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer′s disease: optimization, biological efficacy, and potential toxicity [J]. J Pharm Sci, 2015, 104(10): 3544-3556.
[56]
CHEN Y, CHENG G, HU R, et al. A nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of huperzine A: formulation, evaluation, and in vivo pharmacokinetic study [J]. AAPS Pharm Sci Tech, 2019, 20(7): 301.
[57]
GU F G, FAN H M, CONG Z X, et al. Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride [J]. Acta Pharm, 2020, 70(3): 411-422.
2022, Vol. 57 
